Objectives Uncovering heterogeneities in longitudinal patterns (trajectories) of opioid use among individuals with opioid use disorder can increase our understanding of disease progression and treatment responses to improve care. The present study aims to identify distinctive opioid use trajectories and factors associated with these patterns among participants randomized to treatment with methadone (MET) or buprenorphine + naloxone (BUP). Methods Growth mixture modeling was applied to identify distinctive opioid use trajectories among 795 opioid users after their enrollment in a multi-site trial during 2006–2009, with follow-up interviews conducted in 2011–2014. Results Four distinctive trajectories were identified based on opioid use over the follow-up period: Low Use (42.0%), High Use (22.3%), Increasing Use (17.1%), and Decreasing Use (18.6%). Greater odds of being in the High Use group (relative to Low Use) was associated with Hispanics (relative to African American, OR=3.21), injection drug use (OR=2.12), higher mental health functioning at baseline (OR=1.23), location on the West Coast (vs. East Coast, OR=2.15), and randomization to BUP (relative to MET, OR=1.53). High Use and Increasing Use groups had greater severity in problems related to drug, employment, legal, and social/family relationships, and worsened mental health functioning at follow-up. Participation in treatment significantly accounted for both within- and between-group differences in opioid use. Conclusions Continued treatment is necessary to reduce risk for opioid use and related adverse consequences, particularly among individuals (e.g., injecting drug) at risk for consistently high level of opioid use.